Direct brain recordings reveal continuous encoding of structure in random stimuli

The brain excels at processing sensory input, even in rich or chaotic environments. Mounting evidence attributes this to the creation of sophisticated internal models of the environment that draw on statistical structures in the unfolding sensory input. Understanding how and where this modeling takes place is a core question in statistical learning and predictive processing. In this context, we address the role of transitional probabilities as an implicit structure supporting the encoding of a random auditory stream. Leveraging information-theoretical principles and the high spatiotemporal resolution of intracranial electroencephalography, we analyzed the trial-by-trial high-frequency activity representation of transitional probabilities. This unique approach enabled us to demonstrate how the brain continuously encodes structure in random stimuli and revealed the involvement of a network outside of the auditory system, including hippocampal, frontal, and temporal regions. Linking the frame-works of statistical learning and predictive processing, our work illuminates an implicit process that can be crucial for the swift detection of patterns and unexpected events in the environment.Fil: Fuhrer, Julian. University of Oslo; NoruegaFil: Kyrre, Glette. University of Oslo; NoruegaFil: Ivanovic, Jugoslav. University of Oslo; NoruegaFil: Gunnar Larsson, Pål. University of Oslo; NoruegaFil: Bekinschtein, Tristán Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. University of Cambridge; Reino UnidoFil: Kochen, Sara Silvia. Universidad Nacional Arturo Jauretche. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos; ArgentinaFil: Knight, Robert T.. University of California at Berkeley; Estados UnidosFil: Tørresen, Jim. University of Oslo; NoruegaFil: Solbakk, Anne Kristin. University of Oslo; Noruega. Helgeland Hospital; NoruegaFil: Endestad, Tor. University of Oslo; Noruega. Helgeland Hospital; NoruegaFil: Blenkmann, Alejandro Omar. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. University of Oslo; Norueg

Prefrontal Glutamate Levels Predict Altered Amygdala-prefrontal Connectivity in Traumatized Youths

BACKGROUND:Neurobiological models of stress and stress-related mental illness, including post-traumatic stress disorder, converge on the amygdala and the prefrontal cortex (PFC). While a surge of research has reported altered structural and functional connectivity between amygdala and the medial PFC following severe stress, few have addressed the underlying neurochemistry.METHODS: We combined resting-state functional magnetic resonance imaging measures of amygdala connectivity with in vivo MR-spectroscopy (1H-MRS) measurements of glutamate in 26 survivors from the 2011 Norwegian terror attack and 34 control subjects.RESULTS: Traumatized youths showed altered amygdala-anterior midcingulate cortex (aMCC) and amygdala-ventromedial prefrontal cortex (vmPFC) connectivity. Moreover, the trauma survivors exhibited reduced levels of glutamate in the vmPFC which fits with the previous findings of reduced levels of Glx (glutamate + glutamine) in the aMCC (Ousdal et al.2017) and together suggest long-term impact of a traumatic experience on glutamatergic pathways. Importantly, local glutamatergic metabolite levels predicted the individual amygdala-aMCC and amygdala-vmPFC functional connectivity, and also mediated the observed group difference in amygdala-aMCC connectivity.CONCLUSIONS: Our findings suggest that traumatic stress may influence amygdala-prefrontal neuronal connectivity through an effect on prefrontal glutamate and its compounds. Understanding the neurochemical underpinning of altered amygdala connectivity after trauma may ultimately lead to the discovery of new pharmacological agents which can prevent or treat stress-related mental illness

The impact of traumatic stress on Pavlovian biases

BACKGROUND: Disturbances in Pavlovian valuation systems are reported to follow traumatic stress exposure. However, motivated decisions are also guided by instrumental mechanisms, but to date the effect of traumatic stress on these instrumental systems remain poorly investigated. Here, we examine whether a single episode of severe traumatic stress influences flexible instrumental decisions through an impact on a Pavlovian system. METHODS: Twenty-six survivors of the 2011 Norwegian terror attack and 30 matched control subjects performed an instrumental learning task in which Pavlovian and instrumental associations promoted congruent or conflicting responses. We used reinforcement learning models to infer how traumatic stress affected learning and decision-making. Based on the importance of dorsal anterior cingulate cortex (dACC) for cognitive control, we also investigated if individual concentrations of Glx (=glutamate + glutamine) in dACC predicted the Pavlovian bias of choice. RESULTS: Survivors of traumatic stress expressed a greater Pavlovian interference with instrumental action selection and had significantly lower levels of Glx in the dACC. Across subjects, the degree of Pavlovian interference was negatively associated with dACC Glx concentrations. CONCLUSIONS: Experiencing traumatic stress appears to render instrumental decisions less flexible by increasing the susceptibility to Pavlovian influences. An observed association between prefrontal glutamatergic levels and this Pavlovian bias provides novel insight into the neurochemical basis of decision-making, and suggests a mechanism by which traumatic stress can impair flexible instrumental behaviours

Anterior cingulate cortex and cognitive control: Neuropsychological and electrophysiological findings in two patients with lesions to dorsomedial prefrontal cortex

Whereas neuroimaging studies of healthy subjects have demonstrated an association between the anterior cingulate cortex (ACC) and cognitive control functions, including response monitoring and error detection, lesion studies are sparse and have produced mixed results. Due to largely normal behavioral test results in two patients with medial prefrontal lesions, a hypothesis has been advanced claiming that the ACC is not involved in cognitive operations. In the current study, two comparably rare patients with unilateral lesions to dorsal medial prefrontal cortex (MPFC) encompassing the ACC were assessed with neuropsychological tests as well as Event-Related Potentials in two experimental paradigms known to engage prefrontal cortex (PFC). These included an auditory Novelty Oddball task and a visual Stop-signal task. Both patients performed normally on the Stroop test but showed reduced performance on tests of learning and memory. Moreover, altered attentional control was reflected in a diminished Novelty P3, whereas the posterior P3b to target stimuli was present in both patients. The error-related negativity, which has been hypothesized to be generated in the ACC, was present in both patients, but alterations of inhibitory behavior were observed. Although interpretative caution is generally called for in single case studies, and the fact that the lesions extended outside the ACC, the findings nevertheless suggest a role for MPFC in cognitive control that is not restricted to error monitoring

Sex-specific development of spatial orientation is independent of peripubertal gonadal steroids

Prenatal exposure to androgens has been shown to modulate brain development, resulting in changed behavioral attitudes, sexual orientation and cognitive functions, including processing of spatial information. Whether later changes in gonadotropic hormones during puberty induce further organizational effects within the brain is still insufficiently understood. The purpose of this study was to assess development of spatial orientation before and after the time of normal pubertal development, in an ovine model where half of the animals did not undergo typical reproductive maturation due to the pharmacological blockade of gonadotropin releasing hormone receptor (GnRHR) signaling. The study formed part of a larger trial and utilized 46 pairs of same sex Scottish Mule Texel Cross twins (22 female and 24 male). One twin remained untreated throughout (control) while the other received a subcutaneous GnRH agonist (GnRHa: Goserelin-Acetate) implant every fourth week. GnRHa treatment began at eight and 28 weeks of age, in males and females respectively, because the timing of the pubertal transition is sexually differentiated in sheep as it is in humans. Spatial orientation was assessed at three different time points: eight weeks of age, before puberty and treatment in both sexes; 28 weeks of age, after 20 weeks GnRHa treatment in males and before puberty and GnRHa treatment in females; and at 48 weeks of age, which is after the normal time of the pubertal transition in both sexes. Spatial orientation was tested in a spatial maze with traverse time as the main outcome measure. GnRHa treatment did not affect spatial maze performance as no significant differences in traverse time between treated and untreated animals were observed at any time-point. Adolescent females (48 weeks of age) traversed the maze significantly faster than adolescent males, whereas no sex differences in traverse time were seen at earlier developmental stages (eight and 28 weeks). Development of sex differences in spatial orientation was independent of exposure to pubertal hormones since puberty-blocked and control animals both showed the same pattern of spatial maze performance. This result demonstrates the prenatal nature of spatial orientation development. Furthermore, the unexpected finding that female animals outperformed males in the spatial orientation task, underscores the importance of the testing context in spatial orientation experiments

Lateral prefrontal cortex lesion impairs regulation of internally and externally directed attention

Our capacity to flexibly shift between internally and externally directed attention is crucial for successful performance of activities in our daily lives. Neuroimaging studies have implicated the lateral prefrontal cortex (LPFC) in both internally directed processes, including autobiographical memory retrieval and future planning, and externally directed processes, including cognitive control and selective attention. However, the causal involvement of the LPFC in regulating internally directed attention states is unknown. The current study recorded scalp EEG from patients with LPFC lesions and healthy controls as they performed an attention task that instructed them to direct their attention either to the external environment or their internal milieu. We compared frontocentral midline theta and posterior alpha between externally and internally directed attention states. While healthy controls showed increased theta power during externally directed attention and increased alpha power during internally directed attention, LPFC patients revealed no differences between the two attention states in either electrophysiological measure in the analyzed time windows. These findings provide evidence that damage to the LPFC leads to dysregulation of both types of attention, establishing the important role of LPFC in supporting sustained periods of internally and externally directed attention